Serum metalloproteinases MMP-2, MMP-9, and metalloproteinase tissue inhibitors in patients are associated with arteriovenous fistula maturation

Objective Many vascular surgeons construct arteriovenous fistulas (AVFs) for hemodialysis access as the primary choice access. A significant number of AVFs fail to mature, however, leading to patient frustration and repeated operations. Metalloproteinase (MMP) activity, particularly MMP-2 and MMP-9,...

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Published in:Journal of vascular surgery 2011-08, Vol.54 (2), p.454-460
Main Authors: Lee, Eugene S., MD, PhD, Shen, Qiang, MD, PhD, Pitts, Robert L., BS, Guo, Mingzhang, DVM, PhD, Wu, Mack H., MD, Sun, Sue C., MD, Yuan, Sarah Y., MD, PhD
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Arteriovenous Shunt, Surgical - adverse effects
Biological and medical sciences
Biomarkers - blood
California
Chi-Square Distribution
Enzyme-Linked Immunosorbent Assay
Humans
Injuries of the thorax. Foreign bodies. Diseases due to physical agents
Matrix Metalloproteinase 2 - blood
Matrix Metalloproteinase 9 - blood
Medical sciences
Middle Aged
Prospective Studies
Renal Dialysis
Renal Insufficiency, Chronic - blood
Renal Insufficiency, Chronic - enzymology
Renal Insufficiency, Chronic - therapy
Surgery
Surgery (general aspects). Transplantations, organ and tissue grafts. Graft diseases
Time Factors
Tissue Inhibitor of Metalloproteinase-2 - blood
Tissue Inhibitor of Metalloproteinase-4
Tissue Inhibitor of Metalloproteinases - blood
Traumas. Diseases due to physical agents
Treatment Outcome
Ultrasonography, Doppler, Duplex
United States
United States Department of Veterans Affairs
Up-Regulation
Vascular surgery: aorta, extremities, vena cava. Surgery of the lymphatic vessels
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Summary:Objective Many vascular surgeons construct arteriovenous fistulas (AVFs) for hemodialysis access as the primary choice access. A significant number of AVFs fail to mature, however, leading to patient frustration and repeated operations. Metalloproteinase (MMP) activity, particularly MMP-2 and MMP-9, may be important for AVF maturation. We therefore sought to identify whether serum MMP levels could serve as a biomarker for predicting future successful AVF maturation. Methods Blood was collected from patients with chronic renal insufficiency at the time of surgery for long-term hemodialysis access. Serum was separated from whole blood and ultracentrifuged at 1000 g for 10 minutes. Serum aliquots were frozen at –80°C until used for analysis. Enzyme-linked immunosorbent assay was used to assay levels of MMP-2, MMP-9, and tissue inhibitor of metalloproteinase type 2 (TIMP-2), and TIMP type 4 (TIMP-4). Clinical end points were used to divide patients into failed and matured AVF groups. Successful maturation was considered in patients who had specific duplex findings or 1 month of successful two-needle cannulation hemodialysis. MMP/TIMP ratios were calculated as an index of the MMP axis activity because MMP activity parallels alterations in TIMP levels. Results Of 20 enrolled patients, AVF maturation was successful in 13 and failed in 7. Serum levels of MMP-2/TIMP-2 were significantly higher in patients with matured AVFs vs levels in those that failed ( P = .003). Similarly, a trend toward increased serum levels of MMP-9/TIMP-4 was found in patients with successful AVF ( P = .06). Conclusions MMP-2 and TIMP-2 levels were different among patients whose AVF matured vs those who did not. Further follow-up studies to determine the predictability of AVF maturation using relative patient serum levels of MMP-2 and TIMP-2 should be performed.
ISSN:0741-5214
1097-6809
DOI:10.1016/j.jvs.2011.02.056